Deficiencies in DNA damage response and repair pathways that manage DNA double-strand breaks (DSBs) are associated with cancer susceptibility. For instance, mutations in either BRCA1 or BRCA2, which are involved in DSB repair through interaction with RAD51 proteins, can lead to a greatly increased risk of developing breast, ovarian, and prostate cancers.
The RAD51 protein family provides core components of the Homologous Recombination (HR) complex, which is critical for repairing DNA double-strand breaks and maintaining genome stability. RAD51D, a member of the RAD51 protein family, is required for homology-directed repair of both DNA DSBs and interstrand crosslinks and maintains chromosome and telomere integrity. RAD51D participates in the “BRCA2 complex” and interacts directly with RAD51C and XRCC2.
Better understanding of the regulation of HR proteins by ubiquitylation processes can provide important insights into cancer progression and guide the identification of new therapeutic strategies. For instance, the development of compounds that regulate HR processes, for example through post-translational modification of the RAD51 paralogs would be of benefit in the art. Identified mediators are potential cancer susceptibility markers or possible chemotherapeutic targets.